Case Study-Low testosterone
Patient: 44 year old male complaining of fatigue, low testosterone, and low stress tolerance.
We used the Dutch Complete hormone test, which is an interesting perspective of evaluating hormones discussed. In regards to this client I am discussing, he has low free cortisol and high cortisone, which means his body is converting cortisol to cortisone, inactivating it.
The enzyme that is responsible for this conversion is 11B-HSD2, that plays a crucial role in converting active cortisol into inactive cortisone, conferring specificity (Quinkler and Stewart, 2003). Two distinct isozymes of 11B-hydroxysteroid dehydrogenase (11B-HSD) catalyze the interconversion of hormonally active cortisol and inactive cortisone. In human tissues, the type 1 enzyme (11B-HSD1) is widely distributed but most abundant in liver and adipose tissue. It functions mainly as an oxoreductase converting cortisone to cortisol. Conversely, in adult tissues the type 2 isozyme (11B- HSD2) is found predominantly in mineralocorticoid target tissues, kidney, colon, and salivary gland, where it serves to protect the mineralocorticoid receptor (MR) from glucocorticoid excess (Quinkler and Stewart, 2003). Preference for cortisone is often see in stress, illness, injury or hyperthyroidism. Licorice root is interesting because it can inhibit the 11B HSD2 activity, and it may help him favor producing more cortisol and slow down the inactivation to cortisone, so that the dial can move toward the middle a bit more (Stress and Hormones, 2017). Interesting, grapefruit juice can also inactivate 11B-HSD2 enzyme, and may help in this situation as well.
His Dutch also indicates he has high metabolized cortisol but low free cortisol. An interesting pattern I learned in the FDN Stress and Hormones course is that often times this pattern is mistaken as an adrenal issue, but in reality, it could be a clearance issue. The adrenals have no problem producing cortisol, but the body is choosing not to keep it around as active cortisol, and therefore clearing it too quickly. This pattern can indicate insulin resistance, chronic stress response, chronic fatigue, infections, pain or inflammation. This could actually be a situation where the body is choosing to lower cortisol availability to tissues by clearing it very quickly as a protective measure against high cortisol levels. Often times, this pattern is seen in obesity or where the client may complain of belly fat.
And finally, his low testosterone was his biggest compliant and why he came to me in the first place. We trace that back to low DHEA. DHEA is a steroid hormone produced in the adrenal cortex mainly, and protects the CNS tissues from the catabolic effects of cortisol (Stress and Hormones, 2017). It is a precursor hormone that can be converted to both estrogen and testosterone. Unfortunately, levels also decline with age. Symptoms of low DHEA include fatigue, decreased muscle mass, decrease bone density, depression, aching joints, low libido and low immunity. When cortisol goes up, DHEA should go up to match it (Stress and Hormones, 2017). When looking at the Dutch, one way to compare the Cortisol: DHEA ratio is to look at the dials of the metabolized cortisol with the total DHEA production. A high cortisol to DHEA ratio indicates that metabolized cortisol is significantly higher than total DHEA production. My client has this pattern, as indicated below.
The Dutch displays 3 different markers of DHEA. Total DHEA (which is the sum of 3 markers-DHEA-S, plus the 2 DHEA metabolites etiocholanolone and androsterone), DHEA-S (the sulfated form of DHEA, which occurs when the body needs DHEA), and the two downstream metabolites which can reflect the amount of DHEA being made. The level of the two DHEA metabolites and DHEA-S should be approximately the same (Stress and Hormones, 2017). If they don’t match, this can give clues about what might be going on in the body to upregulate or downregulate the sulfation process. In his case, they actually do match
Looks like low DHEA is the biggest culprit here. So, what is the cause of the low DHEA? It used to be thought that the low DHEA production was due to a concept called “pregnenolone steal”, in which diminished levels are caused by a reduced availability of pregnenolone. However, new theories are modifying this as a “cortisol steal” instead, indicating that reduced DHEA levels may actually be due to it being stolen for cortisol production. The conversion of cholesterol to pregnenolone occurs in the mitochondria of cells and DHEA and cortisol are produced in completely different parts of the adrenal glands, as Christine mentioned above. As a result, “there are no known mechanisms that allow the transfer of pregnenolone between different types of cells” (Stress and Hormones, 2017). Possible causes of low DHEA include stress, inflammation, poor blood sugar regulation, toxic exposure and use of certain medications. Certain substances inhibit the enzyme (17.20 lyase) which is responsible for converting 17 OH-pregnenolone into DHEA in the adrenal glands. Studies indicate that improving blood sugar levels with diet and certain medications can allow for the enzyme activity to correct itself, leading to improved cortisol and DHEA levels. Dioxins in the environment can also inhibit this enzyme. The highest foods sources of dioxins include animal products (Meat, dairy, fish and shellfish). Dioxins are fat soluble and it can bioaccumulate in the food chain. A North American diet will typically expose 93% of dioxin exposure from meat and dairy products. 23% is from milk and dairy alone! The other largest source of exposure is beef, fish, pork, poultry and eggs.
One final thing to point out are the conversion of the metabolites via the 5a reductase or the 5b reductase pathway. This person favored the 5a reductase (see below), which makes the androgens more androgenic, due to excess 5a-DHT production. In this case, it is not a good idea to supplement with DHEA. Often times practitioners will supplement with DHEA, but this can increase 5a reductase activity. If DHEA supplementation is desired, one strategy is to use 5a reductase inhibitors to neutralize the side effects, such as saw palmetto, ECGC, nettles, reishi mushroom, GLA fatty acids, zinc, flax oil, borage oil, black current seed oil, riboflavin. Nutrients include zinc and riboflavin, which can be found in pumpkin seeds, spearmint, green tea, rosemary, MCT oil, coconut oil and flaxseeds. If supplementing with DHEA, look for androgenic symptoms and use the 5a reductase inhibitors to shift androgen metabolism more towards B-pathway. DHEA supplementation should be avoided in people who have breast or prostate cancer.
Other ways to support low DHEA is to support HPA axis, mitochondrial support (such as Mitochondrial NRG) and blood sugar support. It may benefit to run a Micronutrient test to see if there is poor Glucose-Insulin interaction, in which chromium supplementation will help as well. Your adrenal glands require vitamin B-6 and the minerals zinc and magnesium to function properly, so the micronutrient test can detect if additional supplementation is required here as well.
Pomeroy, L. (2017). Stress and Hormones. FDN Training online. [Web based] Retrieved (2018, November 1) from https://www.fdnconnect.com/dashboard/
Quinkler, M., & Stewart, P. M. (2003). Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab, 88(6), 2384-2392. doi:10.1210/jc.2003-030138